Oligodendrocyte Lineage Cell Mechanisms of Axon Selection for Myelination

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PROJECT SUMMARY Oligodendrocytes are the resident myelinating cell type of the central nervous system. Recent work indicates that different classes of neurons have differing patterns and distribution of myelin along their axons. Yet only recently has the identity of the axons been considered with respect to myelination. Thus, the mechanisms of axon signaling and selection for myelination remain largely unknown. Our lab and others have shown that neuronal activity increases myelination and synaptic vesicle release occurs along axons underneath myelin sheaths, suggesting oligodendrocytes may need to be able to receive and interpret neurotransmitter signaling. A single oligodendrocyte can myelinate up to 40 distinct axons, posing a unique situation where an individual cell may need to adapt to signaling from many different neurons. How might this be achieved? Oligodendrocytes express many canonical post-synaptic factors, ostensibly to aid in signaling between the axon and myelin sheath, but the role these proteins play in myelinating cells is largely unknown. Using a zebrafish model, this proposal will utilize genetic approaches and in vivo imaging to address two fundamental concepts: is there a pattern to the expression and/or localization of these post-synaptic factors in oligodendrocytes and does this correspond to wrapped axonal identity; and what function do they serve in the process of myelination. This will be achieved in two aims: Aim 1 tests what post-synaptic factors are expressed, where these post-synaptic proteins localize, and when are they important; and Aim 2 tests how these proteins function to facilitate myelination, and if there is a correlation between axon identity and localization and function of post-synaptic proteins in myelinating oligodendrocytes.